摘要
本研究建立了同时测定人血浆中奥美拉唑（ＯＰＺ）及其代谢物５’－羟基奥美拉唑（５’－ＯＨ－ＯＰＺ）及奥美拉唑砜（ＯＰＺ－ＳＦ）的反相ＨＰＬＣ方法。三个化合物的色谱峰分离良好，其保留时间分别为７，９和１６ｍｉｎ。其平均回收率分别为１０４±４．４，８７．０±４．０和９２．０±１．１％。日内和日间变异系数均小于１０％，最低检测浓度均低于５０ｎｍｏｌ／ｌ。本文又研究了１６名健康志愿者（８名Ｓ－美芬妥英强代谢者和８名Ｓ－美芬妥英弱代谢者）一次口服２０ｍｇ奥美拉唑的药代动力学规律，实验结果发现受试者间血药浓度存在明显个体的差异。根据奥美拉唑血药浓度的差别，将受试者分为强代谢者（ＯＰＺ－ＥＭｓ）和弱代谢者（ＯＰＺ－ＰＭｓ）两组，并分别估算其药代动力学参数。结果表明，奥美拉唑的药代动力学特征均符合一室开放模型，其主要药代动力学参数如下：在强代谢者和弱代谢者中，奥美拉唑的ＡＵＣ分别为３７±３．９μｍｏｌ·ｈ（－１）和１３．０±６．０μｍｏｌ·ｈ（－１）；Ｋｅ分别为０．８９±０．３４和０．２５±０．１０ｈ（－１）；消除ｔ（１／２）分别为０．８５±０．２２和３．３０±１．７８ｈ，两组间均具有显著的差异（Ｐ＜０．０５）。另外发现，弱?
A reversed-phase HPLC method was developed for simutaneous determination ofomeprazole(OPZ) in human plasma, together with two of its metabolites-5-hydroxy-omeprazole andomeprazole sulfone. The separation between omeprazole, its metabolites and the internal standard was quitesufficient in chromatography, The retention time of OPZ,5’-hydroxy-omeprazole(5-OH-OPZ)andomeprazole sulfone(OPZ-SF) was 16. 7 and 9 min, respectively; The detection limit of these 3 compoundsall were <50 nmol / l. The mean recoveries of OP2.5’-OH-OPZ and OPZ-SF were 104±4.4.87.0±4.0 and 92.0±1.0%, respectively. The within day and day to day coefficient of variation were all less than 10%. After a single oral dose of 20 mg OPZ,there was a great interindividual variation in pharmacohnetiesof OPZ in 16 Chinese healthy volunteers (including 8 S-mephenytoin EMs and 8 S-mephenytoin PMs).According to the differences of OPZ plasma concentration, the 16 volunteers were divided into two groups :omeprazole extensive metabolizer( OPZ-EMs) and omeprazole poor metabolizer( OPZ-PMs). The pharmacokinetic parameters of them were calculated separately. A one open compartment model was fitted tothe plasma concentration-time curves of OPZ, OPZ-SF and 5’-OH-OPZ following a single oraladministration of drug, The main pharmacokinetic parameters were followed: the x±s AUC for OPZ inEMs and PMs were 3.7±3.9 and 13.0±6.0μmol·h(-1); Ke was 0.89+0.34 and 0.25+0.10 h(-1) and theclimination t1/2 was 0. 85 ± 0.22 and 3.30 ±1.78 h,respectively, There was a great difference between thetwo groups( P<0. 05-0.001). The AUC and Cmax of the 5 -OH -OPZ were much lower in OPZ-PMsthan in OPZ-EMs. Contrarily, these two parameters of OPZ-SF were iowcr in OPZ-EMs than that inOPZ-PMs. From the results it can be suggested that there were great interindividual differences in thepharmaeokineties of OPZ and its metabolites, cspeciaely there was a polymorphic hydroxylation metabolismof OPZ. Our results also showed that OPZ-PM is correlated to the phenotypes of S-mephenytoin hydroxylation.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
1994年第1期14-21,34,共9页
The Chinese Journal of Clinical Pharmacology
关键词
奥美拉唑
药代动力学
高效液相色谱
omeprazole
5’-Hydroxy-omeprazole
omeprazole sulfone
high petformance liquid chromatograph
hydroxylative polymorphism
